1. Field of the Invention
The invention relates to a membrane holder for membrane adsorber chromatography comprising a housing body with a reception space for at least one layer of adsorber membranes and at least one first housing cap for closing a first reception space opening, which can be fixed to the housing body, a liquid stream being introducible via first liquid guide means through the first housing cap and the first reception opening into the reception space, so that it passes through the adsorber membranes and flows away through a second reception space opening.
2. Description of the Related Art
Membrane adsorber chromatography is widely used both on the laboratory scale and in order to obtain substances in a production process. It is used for the selective separation of substances from a liquid. The basic principle of membrane adsorber chromatography resides in passing a liquid, which contains the substances to be separated, generally through a stack of flat pieces (layers) of porous membrane adsorber material, hereafter abbreviated to adsorber membrane or membranes, which have a selective or preferably specific adsorptivity for the substances to be separated.
According to WO-A1-92/00805 (Sartorius A G), by porous membrane adsorbers is meant those membranes which carry functional groups, ligands or reactants on their surface which are capable of interacting with at least one substance of a liquid phase placed in contact with them. The transport of the liquid phase through the membrane takes place convectively. The term adsorber membrane will be used in the scope of the present invention as a generic term for flat pieces of various types of membrane adsorbers, such as membrane ion exchangers, ligand membranes and activated membranes, which are in turn subdivided into different membrane adsorber types according to the functional groups, ligands and reactants.
Membrane adsorber chromatography is usually carried out as a multistage method, the liquid to be purified being passed through an adsorber membrane stack with the desired adsorption properties in a first step; in a subsequent step, the adsorber membrane stack is flushed with an eluent so that the target substances adsorbed on the membrane are released from the membrane. The resulting eluate, which contains substances to be separated from the original liquid, can then be sent to further treatment or processing steps.
On the laboratory scale, these steps are usually carried out with the aid of the centrifuging technique. For instance, basket-like membrane holder inserts named Vivapure™ for standard centrifuging vessels are known from Vivascience, Hanover. The Vivapure™ inserts have a liquid-tight wall and a perforated bottom, on which an adsorber membrane stack is arranged preferably with wall contact at the stack circumference. In order to fix the adsorber membrane stack or the at least one layer, a hollow cylinder is pressed into the insert above the stack, the outer diameter of the hollow cylinder being dimensioned so that friction with the wall of the insert ensures axial fixing, while the inner diameter of the hollow cylinder is selected to be less than the diameter of the membrane stack so that the latter can be clamped between the hollow cylinder and the bottom of the insert.
After the insert has been introduced into the centrifuging vessel, the insert is filled up to the intended filling level with the liquid to be purified, and then centrifuged, the liquid being pressed through the membrane stack owing to the centrifugal force and flowing out into a lower region of the centrifuging vessel through the perforated bottom of the insert. The subsequent elution step is carried out similarly.
Application of the centrifuging technique has the disadvantage that the pressure with which the liquid is pressed through the membrane stack is set up only by the centrifugal force, which can be controlled only coarsely, so that the pressure actually applied to the membrane stack can be specified only with difficulty or inaccurately. This leads to acceptance problems of the results achieved by the described method with standardization and approval authorities.
The principle of flow membrane adsorber chromatography is known in the field of production, in which case the adsorber membrane stack is integrated in a line system and flowed through for a defined time under defined pressure conditions, which are defined by corresponding pump means. A membrane holder for such a flow system is known from U.S. Pat. No. 4,895,806. This document discloses a membrane holder which is filled with a membrane adsorber stack, sealing rings that are in tight contact with the cylindrical housing body being fitted respectively between packets of a plurality of membrane layers and at the end of the stack. Housing caps, which on the one hand close the reception space inside the housing body and on the other hand compress the membrane stack, are provided above and below the cylindrical housing body. The housing caps are respectively provided with feed and discharge channels. Such a membrane holder is highly suitable for application on the production scale, i.e. with large throughput volumes and correspondingly large diameters of the membrane stacks, so that the unusable dead volume due to the sealing rings at the end of the stacks is negligibly small compared to the membrane surface actually used.
DE 44 32 628 A1 discloses another membrane holder in which the individual membranes, of which the stack is comprised, are configured to be liquid-impermeable in their edge region. Compared with the approach discussed above, this approach avoids the need to use separate sealing rings. A disadvantage, however, is the increased outlay that is required in order to produce the individual membranes. There is furthermore a similar problem as described above in respect of the aforementioned dead volume.
It is an object of the present invention to provide a membrane holder which is suitable for flow chromatography on a small scale and in which, particularly, the dead volume is minimized.